The letter by Dr Laske regarding of our recent publication of the Texas Alzheimer Research Consortium (TARC) serum-based biomarker algorithm for the detection of Alzheimer disease1 outlines 4 specific critiques that are addressed in this response. While decades of research have been devoted to identifying blood-based markers for the detection of AD, this search has largely been met with consistent failure. One possible explanation for the lack of success is the notion that AD is likely a disease of equifinality; specifically, while the endpoint or clinical manifestation may be similar across patients, there are multiple biological pathways (or endophenotypes) leading to disease expression. Therefore, it is unlikely that any single biomarker will provide adequate diagnostic accuracy. Therefore, we took the approach of combining multiple markers across biological pathways and achieved excellent results.